Global estimates suggest that 3.2 million deaths and 3.1% of disability-adjusted life-years are attributable to outdoor air pollution annually. This places exposure to outdoor air pollution among the most important modifiable risk factors for global disease burden. There is, however, substantial uncertainty in this estimate and there remains a critical need to characterize the impacts of air pollution on cardiopulmonary health in populations that reside in both developed and developing countries. This uncertainty stems in part from the limited information available for the effects of fine particulate matter (PM2.5) air pollution on specific cardiopulmonary health impacts (e.g. stroke and reduced lung function); the inadequate characterization of vulnerable populations; and the fact that little to no direct epidemiological evidence is available for the upper portion of exposure-response relationships. Almost all epidemiological studies of cardiopulmonary health effects associated with PM2.5 have been conducted in developed countries, where PM2.5 concentrations are relatively low compared to developing countries. The objective of this research application is to address these significant uncertainties by conducting the first global epidemiological study of PM2.5 air pollution and cardiopulmonary disease by leveraging the Prospective Urban and Rural Epidemiological Study (PURE). This cohort recruited 155,000 individuals residing in 628 communities in 17 countries and 5 continents, with current follow-up completed for four years and continuing for another six years. This research application will add an air pollution component (PURE-AIR) that will use novel satellite-based air pollution estimates, geographic information science (GIS) and ambient air pollution monitoring to characterize community-level PM2.5 concentrations in the 628 PURE communities. Epidemiological analyses (both cross-sectional and longitudinal) will examine important cardiopulmonary outcomes (e.g. myocardial infarction (MI), heart failure, stroke, chronic obstructive pulmonary disease (COPD), and adult onset asthma) as well as lung function change (using repeat individual measures for 50,000 participants that are facilitated by this application). All analyses will control for a comprehensie set of confounding factors (e.g. smoking, occupational exposures, indoor air pollution from biomass use, diet, etc.). PURE-AIR would be a seminal global study that greatly enhances our understanding of the cardiopulmonary health impacts from outdoor air pollution. This information will inform human health risk assessment and reduce morbidity and mortality in the United States and other countries